An industrial process for producing coenzyme Q10, which is conventional in the art, comprises, for example, isolating coenzymes of plant origin, for example of tobacco origin, and adjusting the side chain length thereof by a synthetic method.
It is known that coenzyme Q10 is produced in a wide variety of organisms, from microorganisms, such as bacteria and yeasts, to higher animals and plants. Thus, the process comprising cultivating a microorganism and extracting this substance from cells thereof can be regarded as one of the most efficient process for producing coenzyme Q10 and has actually been employed in commercial production thereof. However, the productivity of such processes can hardly be said to be good, since the yield is low and the procedure is complicated, for instance.
Attempts have also been made to increase the production of coenzyme Q10 by isolating genes involved in the biosynthesis of coenzyme Q10 and amplifying the genes utilizing the recombinant DNA technology. Coenzyme Q10 is formed in vivo in a multistage process comprising complicated reactions in which a number of enzymes are involved. The route of biosynthesis thereof in prokaryotes partially differs from that in eukaryotes. Basically, however, each route comprises three fundamental steps, namely the step of synthesis of decaprenyl diphosphate, which is the source of the prenyl side chain of coenzyme Q10, the step of synthesis of para-hydroxybenzoic acid, which is the source of the quinone ring, and the step of completion of coenzyme Q10 through coupling of these two compounds and successive substituent conversions. Among these reactions, the reaction which determines the side chain length of coenzyme Q10, namely the decaprenyl diphosphate synthase-involving reaction, which is said to be a rate-determining one in the whole biosynthetic reaction route, is considered to be the most important one.
Therefore, for efficient production of coenzyme Q10, it is considered effective to isolate a decaprenyl diphosphate synthase gene, which is the key gene in the biosynthesis of coenzyme Q10, and utilize the same for the purpose of increasing production. As for the gene source, fungi, in which coenzyme Q10 is produced in relatively large amounts, are leading candidates.
So far, decaprenyl diphosphate synthase genes have been isolated from several microorganisms, such as Schizosaccharomyces pombe (JP-A-09-173076) and Gluconobacter suboxydans (JP-A-10-57072). However, the productivity of coenzyme Q10 in these microorganisms cannot be said to be satisfactory, and the cultivation of these microorganisms and the separation/purification of coenzyme Q10 therefrom have not been efficient. It has thus been desired that a microorganism-derived gene for that enzyme, which enables high level production of coenzyme Q10, be isolated.